This is a proposal to determine the role of contact activation of blood by an artificial surface in causing anastomotic hyperplasia and delayed failure of prosthetic arterial grafts. Three drug protocols which selectively block different limbs of the coagulation cascade will be evaluated as interventional modalities for the modification of anastomotic hyperplasia. Using a new and unique model, the effects of contact activation by two commonly used, but biophysically very different materials, will be determined. Products of thrombogenesis (thromboxane A2 and fibrinopeptide A), liberated by contact of the blood with the prosthetic surface will be assessed and correlated with graft material type, flow rate, and maturity of the neointima. The concomitant effects of blood/surface interaction on white blood cells, compliment activation, and platelet micro-macroaggregates will be similarly determined. The effectiveness of the drug protocols in modifying all these aspects of contact activation will be assessed. The knowledge gained will provide a basis for improvement in prosthetic arterial graft design and therapeutic interventions which modify delayed graft failure. This in vivo study may lead to an in vitro method for evaluating prosthetic arterial grafts and therapeutic modalities. Similar mechanisms and products of contact activation have been implicated in the etiology of the adult respiratory distress syndrome as well as in profound septic shock. Therefore, information derived from the study is of broad general interest to surgery as a whole.